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Drug Interactions between amlodipine / celecoxib and atenolol / chlorthalidone

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

atenolol chlorthalidone

Applies to: atenolol / chlorthalidone and atenolol / chlorthalidone

MONITOR: Although they are often combined in clinical practice, diuretics and beta-blockers may increase the risk of hyperglycemia and hypertriglyceridemia in some patients, especially in patients with diabetes or latent diabetes. In addition, the risk of QT interval prolongation and arrhythmias (e.g. torsades de pointes) due to sotalol may be increased by potassium-depleting diuretics.

MANAGEMENT: Monitoring of serum potassium levels, blood pressure, and blood glucose is recommended during coadministration. Patients should be advised to seek medical assistance if they experience dizziness, weakness, fainting, fast or irregular heartbeats, or loss of blood glucose control.

References

  1. Dornhorst A, Powell SH, Pensky J (1985) "Aggravation by propranolol of hyperglycaemic effect of hydrochlorothiazide in type II diabetics without alteration of insulin secretion." Lancet, 1, p. 123-6
  2. Roux A, Le Liboux A, Delhotal B, Gaillot J, Flouvat B (1983) "Pharmacokinetics in man of acebutolol and hydrochlorothiazide as single agents and in combination." Eur J Clin Pharmacol, 24, p. 801-6
  3. Dean S, Kendall MJ, Potter S, Thompson MH, Jackson DA (1985) "Nadolol in combination with indapamide and xipamide in resistant hypertensives." Eur J Clin Pharmacol, 28, p. 29-33
  4. (2002) "Product Information. Lozol (indapamide)." Rhone Poulenc Rorer
  5. Marcy TR, Ripley TL (2006) "Aldosterone antagonists in the treatment of heart failure." Am J Health Syst Pharm, 63, p. 49-58
View all 5 references

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Moderate

atenolol amLODIPine

Applies to: atenolol / chlorthalidone and amlodipine / celecoxib

MONITOR: Additive reductions in heart rate, cardiac conduction, and cardiac contractility may occur when calcium channel blockers are used concomitantly with beta blockers, particularly in patients with ventricular or conduction abnormalities. While this combination may be useful and effective in some situations, potentially serious cardiovascular adverse effects such as congestive heart failure, severe hypotension, and/or exacerbation of angina may occur. The proposed mechanisms include additive slowing in AV conduction, reduced cardiac contractility secondary to beta-blockade, and decreased peripheral vascular resistance secondary to calcium channel blockade. In addition, some calcium channel blockers may inhibit the CYP450 metabolism of hepatically metabolized beta blockers, resulting in increased serum concentrations.

MANAGEMENT: Close clinical monitoring of patient hemodynamic response and tolerance is recommended if a calcium channel blocker is prescribed with a beta blocker, and the dosage of one or both agents adjusted as necessary. The same precaution should be observed when beta blocker ophthalmic solutions are used, since they are systemically absorbed and can produce clinically significant systemic effects even at low or undetectable plasma levels.

References

  1. Henry M, Kay MM, Viccellio P (1985) "Cardiogenic shock associated with calcium-channel and beta blockers: reversal with intravenous calcium chloride." Am J Emerg Med, 3, p. 334-6
  2. Rosenkranz B, Ledermann H, Frolich JC (1986) "Interaction between nifedipine and atenolol: pharmacokinetics and pharmacodynamics in normotensive volunteers." J Cardiovasc Pharmacol, 8, p. 943-9
  3. Tateishi T, Nakashima H, Shitou T, et al. (1989) "Effect of diltiazem on the pharmacokinetics of propranolol, metoprolol and atenolol." Eur J Clin Pharmacol, 36, p. 67-70
  4. Oesterle SN, Alderman EL, Beier-Scott L, Bain DS, Rothman MT, Schroder JS (1986) "Diltiazem and propranolol in combination: hemodynamic effects following acute intravenous administration." Am Heart J, 111, p. 489-97
  5. Yust I, Hoffman M, Aronson RJ (1992) "Life-threatening bradycardic reactions due to beta blocker-diltiazem interactions." Isr J Med Sci, 28, p. 292-4
  6. Hartwell BL, Mark JB (1986) "Combinations of beta blockers and calcium channel blockers: a cause of malignant perioperative conduction disturbances?" Anesth Analg, 65, p. 905-7
  7. Hossack KF (1982) "Conduction abnormalities due to diltiazem." N Engl J Med, 307, p. 953-4
  8. Strauss WE, Egan T, McIntyre KM, Parisi AF (1985) "Combination therapy with diltiazem and propranolol: precipitation of congestive heart failure." Clin Cardiol, 8, p. 363-6
  9. Ohman KP, Weiner L, von Schenck H, Karlberg BE (1985) "Antihypertensive and metabolic effects of nifedipine and labetalol alone and in combination in primary hypertension." Eur J Clin Pharmacol, 29, p. 149-54
  10. Bauer LA, Murray K, Horn JR, et al. (1989) "Influence of nifedipine therapy on indocyanine green and oral propranolol pharmacokinetics." Eur J Clin Pharmacol, 37, p. 257-60
  11. Ronn O, Bengtsson B, Edgar B, Raner S (1985) "Acute haemodynamic effects of felodipine and verapamil in man, singly and with metoprolol." Drugs, 29, p. 16-25
  12. Sinclair NI, Benzie JL (1983) "Timolol eye drops and verapamil: a dangerous combination." Med J Aust, 1, p. 548
  13. Pringle SD, MacEwen CJ (1987) "Severe bradycardia due to interaction of timolol eye drops and verapamil." Br Med J, 294, p. 155-6
  14. Rocha P, Guerret M, David D, Marchand X, Kahn JC (1990) "Kinetics and hemodynamic effects of intravenous nicardipine modified by previous propranolol oral treatment." Cardiovasc Drugs Ther, 4, p. 1525-32
  15. Smith SR, Wilkins MR, Jack DB, Kendall MJ, Laugher S (1987) "Pharmacokinetic interactions between felodipine and metoprolol." Eur J Clin Pharmacol, 31, p. 575-8
  16. Pouleur H, Etienne J, Van Mechelen H, et al. (1984) "Effects of nicardipine or nifedipine added to propranolol in patients with coronary artery disease." Postgrad Med J, 60, p. 23-8
  17. Schoors DF, Vercruysse I, Musch G, Massart DL, Dupont AG (1990) "Influence of nicardipine on the pharmacokinetics and pharmacodynamics of propranolol in healthy volunteers." Br J Clin Pharmacol, 29, p. 497-501
  18. Nievel JG, Havard CW, Douglas-Jones AP (1987) "Comparison of concomitant nicardipine hydrochloride and propranolol with propranolol alone in patients with essential hypertension." Eur J Clin Pharmacol, 33, p. 21-5
  19. Maclean D, Mitchell ET, Coulson RR, Fitzsimons TJ, McDevitt DG (1988) "Atenolol-nifedipine combinations compared to atenolol alone in hypertension: efficacy and tolerability." Br J Clin Pharmacol, 25, p. 425-31
  20. Leon MB, Rosing DR, Bonow RO, Epstein SE (1985) "Combination therapy with calcium-channel blockers and beta blockers for chronic stable angina pectoris." Am J Cardiol, 55, b69-80
  21. Packer M (1989) "Combined beta-adrenergic and calcium-entry blockage in angina pectoris." N Engl J Med, 320, p. 709-18
  22. Strauss WE, Parisi AF (1988) "Combines use of calcium-channel and beta-adrenergic blockers for the treatment of chronic stable angina." Ann Intern Med, 109, p. 570-81
  23. Levine MA, Ogilvie RI, Leenen FH (1988) "Pharmacokinetic and pharmacodynamic interactions between nisoldipine and propranolol." Clin Pharmacol Ther, 43, p. 39-48
  24. Anastassiades CJ (1980) "Nifedipine and beta-blocker drugs." Br Med J, 281, p. 1251-2
  25. Tateishi T, Ohashi K, Fujimura A, Ebihara A (1992) "The influence of diltiazem versus cimetidine on propranolol metabolism." J Clin Pharmacol, 32, p. 1099-104
  26. Vinceneux P, Canal M, Domart Y, Roux A, Cascio B, Orofiamma B, Larribaud J, Flouvat B, Carbon C (1986) "Pharmacokinetic and pharmacodynamic interactions between nifedipine and propranolol or betaxolol." Int J Clin Pharmacol Ther Toxicol, 24, p. 153-8
  27. Takahashi H, Ohashi N, Motokawa K, Sato S, Naito H (1993) "Poisoning caused by the combined ingestion of nifedipine and metoprolol." J Toxicol Clin Toxicol, 31, p. 631-7
View all 27 references

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Moderate

atenolol celecoxib

Applies to: atenolol / chlorthalidone and amlodipine / celecoxib

MONITOR: Nonsteroidal anti-inflammatory drugs (NSAIDs) may attenuate the antihypertensive effect of beta-blockers. The proposed mechanism is NSAID-induced inhibition of renal prostaglandin synthesis, which results in unopposed pressor activity producing hypertension. In addition, NSAIDs can cause fluid retention, which also affects blood pressure. Indomethacin and piroxicam have been reported to have greater attenuating effects than other NSAIDs, and indomethacin effects may be significant in patients with eclampsia.

MANAGEMENT: Patients receiving a beta-blocker who require prolonged (greater than 1 week) concomitant therapy with an NSAID should have blood pressure monitored more closely following initiation, discontinuation, or change of dosage of the NSAID. The interaction is not expected to occur with low doses (e.g., low-dose aspirin) or intermittent short-term administration of NSAIDs.

References

  1. Salvetti A, Pedrinelli R, Alberici P, Magagna A, Abdel-Haq B (1984) "The influence of indomethacin and sulindac on some pharmacological actions of atenolol in hypertensive patients." Br J Clin Pharmacol, 17 Suppl 1, s108-11
  2. Ylitalo P, Pitkajarvi T, Pyykonen ML, Nurmi AK, Seppala E, Vapaatalo H (1985) "Inhibition of prostaglandin synthesis by indomethacin interacts with the antihypertensive effect of atenolol." Clin Pharmacol Ther, 38, p. 443-9
  3. Radack KL, Deck CC, Bloomfield SS (1987) "Ibuprofen interferes with the efficacy of antihypertensive drugs." Ann Intern Med, 107, p. 628-35
  4. Wong DG, Spence JD, Lamki L, Freeman D, McDonald JW (1986) "Effect of non-steroidal anti-inflammatory drugs on control of hypertension by beta-blockers and diuretics." Lancet, 1, p. 997-1001
  5. Durao V, Prata MM, Goncalves LM (1977) "Modification of antihypertensive effect of beta-adrenoceptor-blocking agents by inhibition of endogenous prostaglandin synthesis." Lancet, 2, p. 1005-7
  6. Abate MA, Neely JL, Layne RD, D'Allessandri R (1991) "Interaction of indomethacin and sulindac with labetalol." Br J Clin Pharmacol, 31, p. 363-6
  7. Salvetti A, Arzilli F, Pedrinelli R, Beggi P, Motolese M (1982) "Interaction between oxprenolol and indomethacin on blood pressure in essential hypertensive patients." Eur J Clin Pharmacol, 22, p. 197-201
  8. Durao V, Prata MM, Concalves LM (1977) "Modification of antihypertensive effect of B-adrenoceptor-blocking agents by inhibition of endogenous prostaglandin synthesis." Lancet, 2, p. 1005-7
  9. Hartmann D, Stief G, Lingenfelder M, Guzelhan C, Horsch AK (1995) "Study on the possible interaction between tenoxicam and atenolol in hypertensive patients." Arzneimittelforschung, 45-1, p. 494-8
View all 9 references

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Moderate

chlorthalidone celecoxib

Applies to: atenolol / chlorthalidone and amlodipine / celecoxib

MONITOR: Concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs) and diuretics may adversely affect renal function due to NSAID inhibition of the renal synthesis of prostaglandins that help maintain renal perfusion in dehydrated states. The risk may be increased in patients on dietary sodium restriction. At the same time, hypotensive effect of the diuretics may be reduced because inhibition of prostaglandins can lead to unopposed pressor activity and, consequently, elevation in blood pressure. Natriuretic and diuretic effects may also be reduced, as NSAIDs have been reported to cause sodium and water retention, which may account for the increased risk of congestive heart failure associated with the combination. One study showed an increase in the incidence density of congestive heart failure (in patients over 55 years of age) from 9.3 per 1,000 person-years in patients on diuretics to 23.3 per 1,000 person-years in patients on both diuretic and NSAID therapy. NSAIDs may also increase the risk of hyperkalemia associated with potassium-sparing diuretics.

MANAGEMENT: In patients receiving both diuretic and NSAID therapy, management consists of avoiding dehydration and carefully monitoring the patient's renal function and blood pressure. If renal insufficiency or hyperkalemia develops, both drugs should be discontinued until the condition is corrected.

References

  1. Allan SG, Knox J, Kerr F (1981) "Interaction between diuretics and indomethacin." Br Med J, 283, p. 1611
  2. McCarthy JT, Torres VE, Romero JC, et al. (1982) "Acute intrinsic renal failure induced by indomethacin." Mayo Clin Proc, 57, p. 289-96
  3. Favre L, Glasson P, Vallotton MB (1982) "Reversible acute renal failure from combined triamterene and indomethacin." Ann Intern Med, 96, p. 317-20
  4. Poe TE, Scott RB, Keith JF Jr (1983) "Interaction of indomethacin with furosemide." J Fam Pract, 16, p. 610-6
  5. Ahmad S (1984) "Indomethacin-bumetanide interaction: an alert." Am J Cardiol, 54, p. 246-7
  6. Dixey JJ, Noormohamed FH, Lant AF, Brewerton DA (1987) "The effects of naproxen and sulindac on renal function and their interaction with hydrochlorothiazide and piretanide in man." Br J Clin Pharmacol, 23, p. 55-63
  7. Brater DC, Fox WR, Chennavasin P (1981) "Interaction studies with bumetanide and furosemide: effects of probenecid and of indomethacin on response to bumetanide in man." J Clin Pharmacol, 21, p. 647-53
  8. Smith DE, Brater DC, Lin ET, Benet LZ (1979) "Attenuation of furosemide's diuretic effect by indomethacin: pharmacokinetic evaluation." J Pharmacokinet Biopharm, 7, p. 265-74
  9. Mor R, Pitlik S, Rosenfeld JB (1983) "Indomethacin- and Moduretic--induced hyperkalemia." Isr J Med Sci, 19, p. 535-7
  10. Kaufman J, Hamburger R, Matheson J, Flamenbaum W (1981) "Bumetanide-induced diuresis and natriuresis: effect of prostaglandin synthetase inhibition." J Clin Pharmacol, 21, p. 663-7
  11. Favre L, Glasson P, Riondel A, Vallotton MB (1983) "Interaction of diuretics and non-steroidal anti-inflammatory drugs in man." Clin Sci, 64, p. 407-15
  12. Pedrinelli R, Magagna A, Arzilli F, et al. (1980) "Influence of indomethacin on the natriuretic and renin-stimulating effect of bumetanide in essential hypertension." Clin Pharmacol Ther, 28, p. 722-31
  13. Weinberg MS, Quigg RJ, Salant DJ, Bernard DB (1985) "Anuric renal failure precipitated by indomethacin and triamterene." Nephron, 40, p. 216-8
  14. Furst DE (1988) "Clinically important interactions of nonsteroidal antiinflammatory drugs with other medications." J Rheumatol Suppl, 17, p. 58-62
  15. Gehr T, Sica DA, Steigler BW, Marshall C (1990) "Interaction of triamterene-hydrochlorothiazide (T-H) and ibuprofen (I)." Clin Pharmacol Ther, 47, p. 200
  16. (2002) "Product Information. HydroDIURIL (hydrochlorothiazide)." Merck & Co., Inc
  17. Watkins J, Abbot EC, Hensby CN, Webster J, Dollery CT (1980) "Attenuation of hypotensive effect of propranolol and thiazide diuretics by indomethacin." Br Med J, 281, p. 702-5
  18. Ripley EB, Gehr TW, Wallace H, Wade J, Kish C, Sica DA (1994) "The effect of nonsteroidal agents (NSAIDs) on the pharmacokinetics and pharmacodynamics of metolazone." Int J Clin Pharmacol Ther, 32, p. 12-8
  19. Desaulles E, Schwartz J (1979) "A comparative study of the action of frusemide and methyclothiazide on renin release by rat kidney slices and the interaction with indomethacin." Br J Pharmacol, 65, p. 193-6
  20. Muller FO, Schall R, Devaal AC, Groenewoud G, Hundt HKL, Middle MV (1995) "Influence of meloxicam on furosemide pharmacokinetics and pharmacodynamics in healthy volunteers." Eur J Clin Pharmacol, 48, p. 247-51
  21. Gurwitz JH, Everitt DE, Monane M, et al. (1996) "The impact of ibuprofen on the efficacy of antihypertensive treatment with hydrochlorothiazide in elderly persons." J Gerontol A Biol Sci Med Sci, 51, m74-9
  22. Heerdink ER, Leufkens HG, Herings RM, Ottervanger JP, Stricker BH, Bakker A (1998) "NSAIDs associated with increased risk of congestive heart failure in elderly patients taking diuretics." Arch Intern Med, 158, p. 1108-12
  23. Leary WP, Reyes AJ (1984) "Drug interactions with diuretics." S Afr Med J, 65, p. 455-61
  24. Bennett WM (1997) "Drug interactions and consequences of sodium restriction." Am J Clin Nutr, 65, S678-81
  25. Marcy TR, Ripley TL (2006) "Aldosterone antagonists in the treatment of heart failure." Am J Health Syst Pharm, 63, p. 49-58
  26. Perazella MA (2000) "Drug-induced hyperkalemia: old culprits and new offenders." Am J Med, 109, p. 307-14
View all 26 references

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Minor

chlorthalidone amLODIPine

Applies to: atenolol / chlorthalidone and amlodipine / celecoxib

The antihypertensive effect of amlodipine and thiazide diuretics may be additive. Management consists of monitoring blood pressure during coadministration, especially during the first 1 to 3 weeks of therapy.

References

  1. Kaplan NM (1991) "Amlodipine in the treatment of hypertension." Postgrad Med J, 67 Suppl 5, s15-9

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Drug and food interactions

Moderate

atenolol food

Applies to: atenolol / chlorthalidone

GENERALLY AVOID: Orange juice may moderately reduce the bioavailability of atenolol by interfering with its absorption from the gastrointestinal tract. In a pharmacokinetic study, subjects ingested 200 mL orange juice 3 times daily for 3 days and twice daily on the fourth day, and took 50 mg atenolol with 200 mL orange juice on day 3. The average peak plasma concentration (Cmax) of atenolol fell by 49% and the area under the concentration-time curve (AUC) fell by 40% in comparison to subjects who drank only water. In addition, the presence of food may reduce the bioavailability of atenolol by 20%. The clinical significance is unknown.

MANAGEMENT: Patients treated orally with atenolol should be advised to take atenolol at the same time each day and to avoid consumption of large amounts of orange juice to prevent any undue fluctuations in serum drug levels. Monitoring for altered efficacy of atenolol may be advisable.

References

  1. Lilja JJ, Raaska K, Neuvonen PJ (2005) "Effects of orange juice on the pharmacokinetics of atenolol." Eur J Clin Pharmacol

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Moderate

atenolol food

Applies to: atenolol / chlorthalidone

MONITOR: Many psychotherapeutic and CNS-active agents (e.g., anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, opioids, alcohol, muscle relaxants) exhibit hypotensive effects, especially during initiation of therapy and dose escalation. Coadministration with antihypertensives and other hypotensive agents, in particular vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.

MANAGEMENT: Caution and close monitoring for development of hypotension is advised during coadministration of these agents. Some authorities recommend avoiding alcohol in patients receiving vasodilating antihypertensive drugs. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia.

References

  1. Sternbach H (1991) "Fluoxetine-associated potentiation of calcium-channel blockers." J Clin Psychopharmacol, 11, p. 390-1
  2. Shook TL, Kirshenbaum JM, Hundley RF, Shorey JM, Lamas GA (1984) "Ethanol intoxication complicating intravenous nitroglycerin therapy." Ann Intern Med, 101, p. 498-9
  3. Feder R (1991) "Bradycardia and syncope induced by fluoxetine." J Clin Psychiatry, 52, p. 139
  4. Ellison JM, Milofsky JE, Ely E (1990) "Fluoxetine-induced bradycardia and syncope in two patients." J Clin Psychiatry, 51, p. 385-6
  5. Rodriguez de la Torre B, Dreher J, Malevany I, et al. (2001) "Serum levels and cardiovascular effects of tricyclic antidepressants and selective serotonin reuptake inhibitors in depressed patients." Ther Drug Monit, 23, p. 435-40
  6. Cerner Multum, Inc. "Australian Product Information."
  7. Pacher P, Kecskemeti V (2004) "Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns?" Curr Pharm Des, 10, p. 2463-75
  8. Andrews C, Pinner G (1998) "Postural hypotension induced by paroxetine." BMJ, 316, p. 595
View all 8 references

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Moderate

chlorthalidone food

Applies to: atenolol / chlorthalidone

MONITOR: Many psychotherapeutic and CNS-active agents (e.g., anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, opioids, alcohol, muscle relaxants) exhibit hypotensive effects, especially during initiation of therapy and dose escalation. Coadministration with antihypertensives and other hypotensive agents, in particular vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.

MANAGEMENT: Caution and close monitoring for development of hypotension is advised during coadministration of these agents. Some authorities recommend avoiding alcohol in patients receiving vasodilating antihypertensive drugs. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia.

References

  1. Sternbach H (1991) "Fluoxetine-associated potentiation of calcium-channel blockers." J Clin Psychopharmacol, 11, p. 390-1
  2. Shook TL, Kirshenbaum JM, Hundley RF, Shorey JM, Lamas GA (1984) "Ethanol intoxication complicating intravenous nitroglycerin therapy." Ann Intern Med, 101, p. 498-9
  3. Feder R (1991) "Bradycardia and syncope induced by fluoxetine." J Clin Psychiatry, 52, p. 139
  4. Ellison JM, Milofsky JE, Ely E (1990) "Fluoxetine-induced bradycardia and syncope in two patients." J Clin Psychiatry, 51, p. 385-6
  5. Rodriguez de la Torre B, Dreher J, Malevany I, et al. (2001) "Serum levels and cardiovascular effects of tricyclic antidepressants and selective serotonin reuptake inhibitors in depressed patients." Ther Drug Monit, 23, p. 435-40
  6. Cerner Multum, Inc. "Australian Product Information."
  7. Pacher P, Kecskemeti V (2004) "Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns?" Curr Pharm Des, 10, p. 2463-75
  8. Andrews C, Pinner G (1998) "Postural hypotension induced by paroxetine." BMJ, 316, p. 595
View all 8 references

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Moderate

amLODIPine food

Applies to: amlodipine / celecoxib

MONITOR: Many psychotherapeutic and CNS-active agents (e.g., anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, opioids, alcohol, muscle relaxants) exhibit hypotensive effects, especially during initiation of therapy and dose escalation. Coadministration with antihypertensives and other hypotensive agents, in particular vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.

MANAGEMENT: Caution and close monitoring for development of hypotension is advised during coadministration of these agents. Some authorities recommend avoiding alcohol in patients receiving vasodilating antihypertensive drugs. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia.

References

  1. Sternbach H (1991) "Fluoxetine-associated potentiation of calcium-channel blockers." J Clin Psychopharmacol, 11, p. 390-1
  2. Shook TL, Kirshenbaum JM, Hundley RF, Shorey JM, Lamas GA (1984) "Ethanol intoxication complicating intravenous nitroglycerin therapy." Ann Intern Med, 101, p. 498-9
  3. Feder R (1991) "Bradycardia and syncope induced by fluoxetine." J Clin Psychiatry, 52, p. 139
  4. Ellison JM, Milofsky JE, Ely E (1990) "Fluoxetine-induced bradycardia and syncope in two patients." J Clin Psychiatry, 51, p. 385-6
  5. Rodriguez de la Torre B, Dreher J, Malevany I, et al. (2001) "Serum levels and cardiovascular effects of tricyclic antidepressants and selective serotonin reuptake inhibitors in depressed patients." Ther Drug Monit, 23, p. 435-40
  6. Cerner Multum, Inc. "Australian Product Information."
  7. Pacher P, Kecskemeti V (2004) "Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns?" Curr Pharm Des, 10, p. 2463-75
  8. Andrews C, Pinner G (1998) "Postural hypotension induced by paroxetine." BMJ, 316, p. 595
View all 8 references

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Moderate

atenolol food

Applies to: atenolol / chlorthalidone

ADJUST DOSING INTERVAL: Concurrent administration with calcium salts may decrease the oral bioavailability of atenolol and possibly other beta-blockers. The exact mechanism of interaction is unknown. In six healthy subjects, calcium 500 mg (as lactate, carbonate, and gluconate) reduced the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of atenolol (100 mg) by 51% and 32%, respectively. The elimination half-life increased by 44%. Twelve hours after the combination, beta-blocking activity (as indicated by inhibition of exercise tachycardia) was reduced compared to that with atenolol alone. However, during a 4-week treatment in six hypertensive patients, there was no difference in blood pressure values between treatments. The investigators suggest that prolongation of the elimination half-life induced by calcium coadministration may have led to atenolol cumulation during long-term dosing, which compensated for the reduced bioavailability.

MANAGEMENT: It may help to separate the administration times of beta-blockers and calcium products by at least 2 hours. Patients should be monitored for potentially diminished beta-blocking effects following the addition of calcium therapy.

References

  1. Kirch W, Schafer-Korting M, Axthelm T, Kohler H, Mutschler E (1981) "Interaction of atenolol with furosemide and calcium and aluminum salts." Clin Pharmacol Ther, 30, p. 429-35

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Moderate

amLODIPine food

Applies to: amlodipine / celecoxib

MONITOR: Calcium-containing products may decrease the effectiveness of calcium channel blockers by saturating calcium channels with calcium. Calcium chloride has been used to manage acute severe verapamil toxicity.

MANAGEMENT: Management consists of monitoring the effectiveness of calcium channel blocker therapy during coadministration with calcium products.

References

  1. Henry M, Kay MM, Viccellio P (1985) "Cardiogenic shock associated with calcium-channel and beta blockers: reversal with intravenous calcium chloride." Am J Emerg Med, 3, p. 334-6
  2. Moller IW (1987) "Cardiac arrest following intravenous verapamil combined with halothane anaesthesia." Br J Anaesth, 59, p. 522-6
  3. Oszko MA, Klutman NE (1987) "Use of calcium salts during cardiopulmonary resuscitation for reversing verapamil-associated hypotension." Clin Pharm, 6, p. 448-9
  4. Schoen MD, Parker RB, Hoon TJ, et al. (1991) "Evaluation of the pharmacokinetics and electrocardiographic effects of intravenous verapamil with intravenous calcium chloride pretreatment in normal subjects." Am J Cardiol, 67, p. 300-4
  5. O'Quinn SV, Wohns DH, Clarke S, Koch G, Patterson JH, Adams KF (1990) "Influence of calcium on the hemodynamic and anti-ischemic effects of nifedipine observed during treadmill exercise testing." Pharmacotherapy, 10, p. 247
  6. Woie L, Storstein L (1981) "Successful treatment of suicidal verapamil poisoning with calcium gluconate." Eur Heart J, 2, p. 239-42
  7. Morris DL, Goldschlager N (1983) "Calcium infusion for reversal of adverse effects of intravenous verapamil." JAMA, 249, p. 3212-3
  8. Guadagnino V, Greengart A, Hollander G, Solar M, Shani J, Lichstein E (1987) "Treatment of severe left ventricular dysfunction with calcium chloride in patients receiving verapamil." J Clin Pharmacol, 27, p. 407-9
  9. Luscher TF, Noll G, Sturmer T, Huser B, Wenk M (1994) "Calcium gluconate in severe verapamil intoxication." N Engl J Med, 330, p. 718-20
  10. Bar-Or D, Gasiel Y (1981) "Calcium and calciferol antagonise effect of verapamil in atrial fibrillation." Br Med J (Clin Res Ed), 282, p. 1585-6
  11. Lipman J, Jardine I, Roos C, Dreosti L (1982) "Intravenous calcium chloride as an antidote to verapamil-induced hypotension." Intensive Care Med, 8, p. 55-7
  12. McMillan R (1988) "Management of acute severe verapamil intoxication." J Emerg Med, 6, p. 193-6
  13. Perkins CM (1978) "Serious verapamil poisoning: treatment with intravenous calcium gluconate." Br Med J, 2, p. 1127
  14. Moroni F, Mannaioni PF, Dolara A, Ciaccheri M (1980) "Calcium gluconate and hypertonic sodium chloride in a case of massive verapamil poisoning." Clin Toxicol, 17, p. 395-400
View all 14 references

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Minor

amLODIPine food

Applies to: amlodipine / celecoxib

The consumption of grapefruit juice may slightly increase plasma concentrations of amlodipine. The mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. Data have been conflicting and the clinical significance is unknown. Monitoring for calcium channel blocker adverse effects (e.g., headache, hypotension, syncope, tachycardia, edema) is recommended.

References

  1. Bailey DG, Arnold JMO, Spence JD (1994) "Grapefruit juice and drugs - how significant is the interaction." Clin Pharmacokinet, 26, p. 91-8
  2. Josefsson M, Zackrisson AL, Ahlner J (1996) "Effect of grapefruit juice on the pharmacokinetics of amlodipine in healthy volunteers." Eur J Clin Pharmacol, 51, p. 189-93
  3. Bailey DG, Malcolm J, Arnold O, Spence JD (1998) "Grapefruit juice-drug interactions." Br J Clin Pharmacol, 46, p. 101-10
  4. Vincent J, Harris SI, Foulds G, Dogolo LC, Willavize S, Friedman HL (2000) "Lack of effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of amlodipine." Br J Clin Pharmacol, 50, p. 455-63
  5. Josefsson M, Ahlner J (2002) "Amlodipine and grapefruit juice." Br J Clin Pharmacol, 53, 405; discussion 406
  6. Kane GC, Lipsky JJ (2000) "Drug-grapefruit juice interactions." Mayo Clin Proc, 75, p. 933-42
View all 6 references

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.


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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.